Ma Qing, Yang Chaoai, Jiang Xu, Liu Jingyu, Shi Yixiang, Li Hui, Liu Hang, Yang Jijin
Interventional Department, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
J Interv Med. 2019 Apr 30;1(3):143-149. doi: 10.19779/j.cnki.2096-3602.2018.03.03. eCollection 2018 Aug.
To investigate the efficacy, safety, and associated mechanisms of injected ozonated saline in the treatment of VX2 tumors. A total of 90 rabbits bearing VX2 tumors on their left hind legs were randomly divided into three groups. The control group (A) received normal saline, while groups B and C received 20 μg/mL and 40 μg/mL O/O ozonated saline, respectively. Rabbits were anesthetized and 2 mL of blood was drawn directly from the heart to measure serum concentrations of interleukin (IL-6) and tumor necrosis factor (TNF-α). The skin covering the VX2 tumor was cut in each rabbit and the maximum and vertical diameters of the tumors were measured under direct visualization. Several milliliters of saline, saline pre-treated with 20 μg/mL O/O, or saline pre-treated with 40 μg/mL O/O were directly injected into the tumors of groups A, B, and C, respectively (injection volume (milliliter) =1/2 volume of the tumor, V = 1/2ab). On days 4, 8 and 12 following treatment, 10 rabbits were randomly selected from each group for blood sample collection, and serum IL-6 and TNF-α were measured. The tumor growth rate was calculated by measuring the maximum and vertical diameters of the VX2 tumors under direct visualization. All selected rabbits were euthanized and the tumors, livers, and lungs were removed for pathological examination. The tumor necrosis rate was calculated by cutting the tumors into half along the longitudinal axis and measuring the maximum diameters of the intratumoral necrotic regions. The average tumor volume in the three groups increased to different degrees at each time point; however, the average tumor growth rates in groups B and C were substantially lower than that in group A, exhibiting a statistically significant difference. The difference in the tumor growth rate between group B and group C was not statistically significant. The serum concentrations of IL-6 and TNF-α increased in the three groups at each time point, with larger increases occurring in groups B and C; however, the greater increases did not reach statistical significance. Although the diameters of the necrotic areas were larger in both groups B and C than that in group A, significant differences in necrotic area diameters were only found when comparing groups A and C on days 4 and 12 following treatment. Direct injection of different concentrations of ozonated saline into VX2 tumors significantly increased intratumoral necrosis and reduced the tumor growth rate. The associated mechanism may be partially mediated by IL-6 and TNF-α, as the serum concentrations of these molecules increased after the treatment.
探讨注射用臭氧生理盐水治疗VX2肿瘤的疗效、安全性及相关机制。将90只左后肢荷VX2肿瘤的家兔随机分为三组。对照组(A组)给予生理盐水,B组和C组分别给予20μg/mL和40μg/mL的O/O臭氧生理盐水。将家兔麻醉后,直接从心脏抽取2mL血液,测定血清白细胞介素(IL-6)和肿瘤坏死因子(TNF-α)浓度。切开每只家兔覆盖VX2肿瘤的皮肤,在直视下测量肿瘤的最大直径和垂直直径。分别向A、B、C组肿瘤内直接注射几毫升生理盐水、用20μg/mL O/O预处理的生理盐水或用40μg/mL O/O预处理的生理盐水(注射体积(毫升)=肿瘤体积的1/2,V = 1/2ab)。在治疗后的第4、8和12天,每组随机选取10只家兔采集血样,测定血清IL-6和TNF-α。通过在直视下测量VX2肿瘤的最大直径和垂直直径来计算肿瘤生长率。对所有选取的家兔实施安乐死,取出肿瘤、肝脏和肺进行病理检查。将肿瘤沿纵轴切成两半,测量瘤内坏死区域的最大直径,计算肿瘤坏死率。三组在各时间点的平均肿瘤体积均有不同程度增加;然而,B组和C组的平均肿瘤生长率显著低于A组,差异具有统计学意义。B组和C组之间的肿瘤生长率差异无统计学意义。三组在各时间点的血清IL-6和TNF-α浓度均升高,B组和C组升高幅度更大;然而,更大幅度的升高未达到统计学意义。虽然B组和C组的坏死区域直径均大于A组,但仅在治疗后第4天和第12天比较A组和C组时,坏死区域直径存在显著差异。向VX2肿瘤内直接注射不同浓度的臭氧生理盐水可显著增加瘤内坏死并降低肿瘤生长率。相关机制可能部分由IL-6和TNF-α介导,因为治疗后这些分子的血清浓度升高。